Refractive corrector incorporating a continuous central phase zone and peripheral phase discontinuities

ABSTRACT

Described refractive correctors, include, but are not limited to, intraocular lenses (IOLs), contact lenses, corneal inlays, and other optical components or devices, incorporating a continuous central phase zone and peripheral phase discontinuities. Further embodiments are directed to a method for using a laser to modify the refractive properties of refractive correctors to form such continuous central phase zone and peripheral phase discontinuities, and other applications. The refractive corrector and methods adapt a Fresnel lens structure to include continuous phase retarding regions having a wavefront height of greater than one design wavelength in a central zone of a refractive corrector to improve human vision applications, while maintaining benefits of phase wrapping in the peripheral region.

BACKGROUND

The disclosure is directed towards refractive correctors including, butare not limited to, intraocular lenses (IOLs), contact lenses, cornealinlays, and other optical components or devices, incorporating acontinuous central phase zone and peripheral phase discontinuities.Further embodiments are directed to a method for using a laser to modifythe refractive properties of refractive correctors to form suchcontinuous central phase zone and peripheral phase discontinuities, andother applications.

In general, there are two types of intraocular lenses, referred to aspseudo-phakic IOLs and phakic IOLs. The former type replaces the eye'snatural, crystalline lens, usually to replace a cataractous lens thathas been removed. The latter type is used to supplement an existing lensand functions as a permanent corrective lens, which is implanted in theanterior or posterior chamber to correct refractive errors of the eye.Common techniques for forming intraocular lenses include molding, ormachining such as by lathing and milling, to form a lens with desiredshape and power. The power of the lens (i.e., point focus on the retinafrom light originating at infinity) to be implanted is determined basedon pre-operative measurements of ocular length and corneal curvature ofeach patient. The pre-operative measurements are conducted with the hopethat the patient will need little, if any, vision correction followingthe surgery. Unfortunately, due to errors in measurement, variable lenspositioning, or wound healing, most patients undergoing surgery will notenjoy optimal vision without some form of vision correction followingthe surgery. Since the power of a typical (non-accommodating) IOL isfixed and cannot be adjusted post-implantation (in-situ), most patientsmust use corrective lenses such as eye glasses or contact lensesfollowing cataract surgery to optimize their vision.

One potential alternative to post-operative, corrective lenses is alight-adjustable intraocular lens whose refractive properties can bemodified following insertion of the lens into a human eye. One suchlens, e.g., is reported in U.S. Pat. No. 6,450,642, wherein thelight-adjustable lens is said to comprise (i) a first polymer matrix and(ii) a refraction modulating composition (RMC) that is capable ofstimulus-induced polymerization. As stated, when a portion of thedescribed lens is exposed to light of sufficient intensity, the RMCforms a second polymer matrix. The process results in a light adjusted,power-modified lens, wherein the power of the lens is changed by a shapechange caused by migration of the RMC and subsequent polymerization(s).

U.S. Pat. No. 7,105,110 describes a method and instrument to irradiate alight adjustable lens as described in the Calhoun Patent with anappropriate amount of radiation in an appropriate pattern. The method issaid to include aligning a source of the modifying radiation so as toimpinge the radiation onto the lens in a pattern, and controlling thequantity of the impinging radiation. The quantity of the impingingradiation is controlled by controlling the intensity and duration of theirradiation.

As opposed to modifying the shape of a lens to change its power, U.S.Publication No. 2008/0001320 describes methods for modifying therefractive index of optical polymeric materials using very short pulsesfrom a visible or near-IR laser having a pulse energy from 0.5 nJ to1000 nJ, where the intensity of light is sufficient to change therefractive index of the material within the focal volume, whereasportions just outside the focal volume are minimally affected by thelaser light. Irradiation within the focal volume results in refractiveoptical structures characterized by a positive change in refractiveindex of 0.005 or more relative to the index of refraction of the bulk(non-irradiated) polymeric material. Under certain irradiationconditions and in certain optical materials, a change in refractiveindex of 0.06 was measured. The irradiated regions of the opticalmaterial can take the form of two- or three-dimensional, area or volumefilled refractive structures. The refractive structures are formed byscanning the laser over a select region of the polymeric materialresulting in refractive optical structures that can provide spherical,aspherical, toroidal, or cylindrical correction to a lens. In fact, anyoptical structure can be formed to yield positive or negative powercorrections to the lens. Moreover, the optical structures can be stackedvertically or written in separate planes in the polymeric material toact as a single lens element. U.S. Pat. No. 7,789,910 further describesusing Raman spectroscopy as an investigative approach to determine what,if any, structural, chemical or molecular change is occurring within thefocal volume of the optical polymeric materials that might explain theobserved change in the index of refraction.

U.S. Publication No. 2009/0287306 describes a similar process to providedioptric power changes in optical polymeric materials that contain aphotosensitizer. The photosensitizer is present in the polymericmaterial to enhance the photoefficiency of the two-photon process usedto form the refractive structures. In some instances, the rate at whichthe laser light is scanned across the polymeric material can beincreased 100-fold with the inclusion of a photosensitizer and stillprovide a similar change in the refractive index of the material.

U.S. Publication No. 2009/0157178 is said to describe a polymericintraocular lens material that can provide a photoinduced, chemicalchange in the material resulting in a change in focal length (power) orthe aspheric character of the lens by modifying the index of refractionof the material with laser light. The photoinduced chemistry in thematerial is said to occur by exposure of the material to laser lightover a broad spectral range of 200 nm to 1500 nm.

U.S. Publication No. 2010/0228345 is said to describe a lens such as anintraocular lens in which the refractive index within a laser focus(loci) are modified to a depth of 5 μm to 50 μm. The method is said toprovide dioptric power changes to the lens by a change in refractiveindex (Δn) of the lens material at different locus positions, e.g.,between a lowest value of Δn=0.001 to a highest value of Δn=0.01. U.S.Publication No. 2010/0228345 further proposes to employ a modulo 2πphase wrapping technique across the lens surface, whereby onlyindividual phase shifts of 0-2π are written across the lens. Thedescribed irradiation method uses bursts of femtosecond (fs) laserpulses to change the refractive index of the irradiated material througha multiphoton absorption mechanism.

U.S. Publication No. 2012/0310340 describes a method for providingchanges in refractive power of an optical device made of an optical,polymeric material by forming at least one laser-modified, gradientindex (GRIN) layer disposed between an anterior surface and a posteriorsurface of the device by scanning with light pulses from a visible ornear-IR laser along regions of the optical, polymeric material. The atleast one laser-modified GRIN layer comprises a plurality of adjacentrefractive segments, and is further characterized by a variation inindex of refraction of at least one of: (i) a portion of the adjacentrefractive segments transverse to the direction scanned; and (ii) aportion of refractive segments along the direction scanned. U.S.Publication 2012/0310223 discloses a method of modifying the refractiveindex in ocular tissues wherein a laser-modified gradient index (GRIN)layer is formed directly in at least one of the corneal stroma and thecrystalline lens. U.S. 2012/0310340 and 2010/0310223 each furtherdiscloses that the design of the gradient index structures can bemodified to provide a phase shift that is modulo-2π to reduce the totaldevice writing times.

Writing a phase shift profile in modulo-2π form is done by subtracting aconstant phase shift of 2π from the total design phase shift in theregions where the total design phase shift is between 2π and 4π,subtracting a constant 4π phase shift from the total design phase shiftin the regions where the total design phase shift is in the range 4π to6π, etc., in a “Fresnel” lens type pattern so that only resulting netphase shifts of 0-2π need to be written. Augustin-Jean Fresnel is widelycredited with inventing the Fresnel lens for lighthouse applications. AFresnel lens is much thinner and lighter than a continuous profile glasslens of the same diameter and focal length, since much of the bulk ofthe glass is removed by Fresnel's design. The concept of the Fresnellens is shown in FIG. 1B, for a corresponding conventional continuousrefractive lens shown in FIG. 1A (reproduced from “The Phase FresnelLens,” K. Miyamoto, JOSA 51, 1, p. 17 (1959)). A continuous phase frontis sampled into increments of 2π phase shift based on a designwavelength λ and a discontinuous phase structure is produced. In thistype of Fresnel lens design, the sampled phase regions occupy the entirelens surface and the phase discontinuities do not exceed 2π anywhere. Inthe conventional kind of Fresnel lens as described by Miyamoto, it canbe advantageous in the fabrication procedure to only have to createphase shifts up to 2π, however such a lens fundamentally has a largechromatic aberration which can be undesirable if not being used tocorrect for other chromatic aberrations in a system.

In order to obtain multi-focality which can be helpful in cases ofpresbyopia, it has been proposed and demonstrated that refracting baselenses can be augmented by placing diffractive steps across the lensdiameter, or selectively either into a central region of the lens (see,e.g., “History and development of the apodized diffractive intraocularlens,” J. A. Davison, M. J. Simpson, J Cataract and Refractive Surgery,VOL 32, p. 849, (2006)), or into an outer peripheral region of the lens(see, e.g., US 2010/0131060). When added selectively to the centralregion, e.g., in high light levels the contraction of the pupileffectively apodizes the lens, allowing light to pass through only thecentral diffractive step zone region. To obtain multi-focality, thephase shift profile is not in modulo-2π form; rather the diffractivesteps in such lenses have phase shifts of less than 2π so thatcollimated light is out of phase between such steps.

There is an ongoing need for new and improved techniques and materials,and refractive corrector vision components resulting therefrom, forimproving human vision. Such components may include IOLs for usefollowing cataract surgery, or may be in the form of corneal inlays orother implantable vision correction devices. There are also advantagesand benefits that would result from such techniques and componentsallowing in-situ modification of refractive properties (e.g., refractiveindex, dioptric power) of such components, as well as directmodification of ocular tissue to provide corrected vision.

SUMMARY

According to aspects illustrated herein, there is provided a refractivecorrector comprising:

(a) a central zone having a continuous wavefront cross-section phaseprofile, having a wavefront maximum height of greater than 1 designwavelength a, in the area of the central zone; and

(b) a peripheral region comprising multiple segments and having adiscontinuous wavefront cross-section phase profile having phase shiftsbetween segments that are equal to the design wavelength or multiples ofthe design wavelength, and wherein the phase shifts in the peripheralregion are less than or equal to the wavefront maximum height in thecentral zone.

According to other aspects, a method of forming a refractive correctoris described comprising:

providing an optical, polymeric lens material having an anterior surfaceand posterior surface and an optical axis intersecting the surfaces; and

forming at least one laser-modified layer disposed between the anteriorsurface and the posterior surface with light pulses from a laser byscanning the light pulses along regions of the optical, polymericmaterial to cause changes in the refractive index of the polymeric lensmaterial;

wherein the optical, polymeric lens material comprises (a) a centralzone having a continuous wavefront cross-section phase profile, having awavefront maximum height of greater than 1 design wavelength λ in thearea of the central zone, and (b) a peripheral region comprisingmultiple segments and having a discontinuous wavefront cross-sectionphase profile having phase shifts between segments that are equal to thedesign wavelength or multiples of the design wavelength, wherein thephase shifts in the peripheral region are less than or equal to thewavefront maximum height in the central zone;

and wherein the at least one laser-modified layer forms at least part ofat least one of the central zone or the peripheral region.

According to other aspects, a method for modifying a refractive propertyof ocular tissue in an eye is described, comprising:

forming at least one optically-modified layer in at least one of thecorneal stroma and the crystalline lens ocular tissue in an eye byscanning light pulses from a laser focused in the corneal stroma orcrystalline lens ocular tissue along regions of the corneal stroma orcrystalline lens ocular tissue to cause changes in the refractive indexwithin the ocular tissue to form a modified corneal stroma orcrystalline lens;

wherein the modified corneal stroma or crystalline lens comprises (a) acentral zone having a continuous wavefront cross-section phase profile,having a wavefront maximum height of greater than 1 design wavelength λin the area of the central zone, and (b) a peripheral region comprisingmultiple segments and having a discontinuous wavefront cross-sectionphase profile having phase shifts between segments that are equal to thedesign wavelength or multiples of the design wavelength, wherein thephase shifts in the peripheral region are less than or equal to thewavefront maximum height in the central zone;

and wherein the at least one optically-modified layer forms at leastpart of at least one of the central zone or the peripheral region.

In various embodiments, the central zone has a phase height greater thanthe phase shifts in the peripheral region.

In various embodiments, the peripheral region has a Fresnel structurehaving a phase shift between segments equal to the design wavelength.

In various embodiments, the peripheral region may more specificallycircumscribe the central zone.

In various embodiments, an outer perimeter of the central zone and anouter perimeter of the peripheral region may be circular.

In various embodiments, an optical surface of the central zone morespecifically may be parabolic, may be hyperbolic, may be a freeformsurface, or may be aspheric.

In various embodiments, the central zone may have an outer diameter ofat least 10, at least 20, at least 25, or at least 30% of the outerdiameter of the peripheral region, e.g., from 10% to 90%, from 20% to80%, from 25% to 75%, or from 30% to 70% of the outer diameter of theperipheral region.

In various embodiments the refractive corrector may be a contact lens oran intra-ocular lens.

In various embodiments, the peripheral region may have a phase profilesampled into 2π phase discontinuities.

In various embodiments, at least one of the central zone or peripheralregion may comprise materials of varying refractive index contributingto the wavefront cross-section phase profile.

In various embodiments, the refractive corrector may be mono-focal forthe design wavelength.

In various embodiments, the design wavelength may be a wavelengthbetween 400 nm and 700 nm.

In various embodiments the design wavelength may be 555 nm.

The refractive corrector and method disclosed herein advantageouslyapply the basic Fresnel lens idea to a new area of human visioncorrection, by adapting the Fresnel lens structure to include continuousphase retarding regions having a wavefront height of greater than 1design wavelength in a central zone of a refractive corrector. Based onour evaluation of the visual effects resulting from the use of thisdesign, we have found that it is advantageous for human visionapplications to include such a continuous phase central zone into adiscontinuous phase Fresnel-type refractive corrector structure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B (Prior Art) provide an illustration of a modulo-2π phasewrapped Fresnel lens (FIG. 1B), for a corresponding conventionalcontinuous refractive lens (FIG. 1A).

FIG. 2 is a schematic of a laser system which may be used for writing awavefront cross-section phase profile in a refractive corrector inaccordance with an embodiment.

FIG. 3 schematically illustrates a hybrid continuous/Fresnel refractivecorrector in accordance with an embodiment.

FIGS. 4A-4C schematically illustrate wavefront cross-sections ofcontinuous, hybrid and Fresnel designs of parabolic phase shiftrefractive correctors.

FIG. 5 illustrates calculated polychromatic retinal image quality forrefractive correctors for a range of positive dioptric powers anddegrees of mixed, continuous and Fresnel type phase profiles.

FIGS. 6A and 6B are graphs of the weighting-coefficient V_(λ) specifiedby the human eye's spectral sensitivity used in calculation of thepolychromatic Strehl ratio, and of the longitudinal chromatic aberrationof the eye)(C₂ ⁰) used in calculating the relative defocus W(λ), alsoused in calculating the polychromatic Strehl ratio.

FIGS. 7A, 7B and 7C schematically illustrate wavefront cross-sections ofparabolic phase shift refractive correctors having various phase-wrapwavefront heights and number of discrete wavefront steps.

FIG. 8 is a graph depicting predicted visual acuity for a range ofdioptric powers for Fresnel, hybrid and continuous lens designs.

FIG. 9 schematically illustrates a wavefront cross-section of arefractive corrector in accordance with an embodiment.

DETAILED DESCRIPTION

Custom refractive correctors may be written into contact lenses,intra-ocular lenses or directly into the cornea. The time required forsuch a writing procedure depends on how much total phase accumulation isrequired to create the desired refractive correction. Any medicalprocedure in humans will have time limits imposed by various factors,including safety, practicality, etc. In such a case, the use ofFresnel-type phase wrapped designs for the refractive corrector can beadvantageous, since it enables writing the equivalent of a desiredconventional continuous refractive phase shift pattern having a totalmaximum phase shift of greater than 2π in a refractive corrector withonly a maximum net phase shift of 2π. Conventional continuous refractinglenses, however, have certain advantages over discontinuous Fresnel-typecorrectors. For instance, they have significantly lower chromaticaberration than Fresnel-type correctors, since they are simply limitedby material dispersion. Furthermore they can in principle exhibit higheroptical quality including lower scattering losses compared toFresnel-type structures if the Fresnel-type structures do not haveperfect phase discontinuities.

In accordance with various disclosed embodiments, designs and methodsfor implementing mixed Fresnel-type refractive correctors are describedthat incorporate a central zone of continuous phase shift, and aperipheral Fresnel-type discontinuous phase shifting region. The centralzone of continuous phase shift more particularly has a continuouswavefront cross-section phase profile, having a wavefront maximum heightof greater than 1 design wavelength λ in the area of the central zone.Thus, the central zone differs from the central zone in a conventionalmodulo 2π phase wrapped refractive corrector. The peripheraldiscontinuous phase shifting region, on the other hand, moreparticularly comprises multiple segments and having a discontinuouswavefront cross-section phase profile having phase shifts betweensegments that are equal to the design wavelength (consistent with aconventional modulo 2π phase rapped region), or multiples of the designwavelength. Further, the phase shifts in the peripheral region are lessthan or equal to the wavefront maximum height in the central zone. Whenthe central zone has a phase height greater than the phase shifts in theperipheral region, the combined advantages of providing a significantcentral continuous zone while still enabling decreased write time forthe combined continuous and discontinuous sections may be achieved. Whenthe peripheral region has phase shifts between segments that are equalto the design wavelength (i.e., where the peripheral region has a phaseprofile sampled into 2π phase discontinuities), the further advantage ofminimizing write time in the peripheral region may be achieved.

In various embodiments, the peripheral region may more specificallycircumscribe the central zone. In further embodiments, an outerperimeter of the central zone and an outer perimeter of the peripheralregion may be circular. In further non-limiting embodiments, an opticalsurface of the central zone further more specifically may be parabolic,may be hyperbolic, may be a freeform surface, or may be aspheric. Forrefractive correctors intended for visual correction, the designwavelength may be, e.g., in the visible range of between 400 and 700 nm,and in particular embodiments within the range of from 500-600 nm, oreven more specifically within the range of from 550-560. Moreparticularly, the design wavelength for the refractive corrector may be,e.g., 555 nm.

As the phase shifts between segments of the peripheral region aredesigned to be equal to the design wavelength or multiples of the designwavelength, the discontinuous peripheral region of the describedrefractive correctors is itself not designed to form a diffractivepattern generating distinct foci at different distances, and thus is notdesigned to provide multi-focality. Accordingly, in particularembodiments, the refractive corrector is designed to be mono-focal for adesign wavelength of the refractive corrector. In further embodiments,however, further design features may be incorporated into the refractivecorrector if desired to additionally provide multi-focality.

In various embodiments, at least one of the central zone or peripheralregion of the refractive corrector may comprise materials of varyingrefractive index contributing to the wavefront cross-section phaseprofile, or may comprise materials of constant refractive index. Moreparticularly, the wavefront cross-section phase profile in the centralzone and peripheral region of the refractive corrector may beestablished by varying the thickness of a material of constantrefractive index across the central zone and peripheral region, byvarying the refractive index of the materials forming such central zoneand peripheral region across such central zone and peripheral region, orby any combination of varying the thickness of the materials and therefractive index of the materials over each of the central zone andperipheral regions. In particular embodiments, the wavefrontcross-section phase profile in the central zone and peripheral region ofthe refractive corrector is established at least in part by varying therefractive index of the materials forming at least one of such centralzone and peripheral region across at least one of such central zone andperipheral region. In further embodiments, the wavefront cross-sectionphase profile in the central zone and peripheral region of therefractive corrector is established at least in part by varying therefractive index of the materials forming each of such central zone andperipheral region across each of such central zone and peripheralregion.

In various embodiments, the central continuous zone and discontinuousperipheral region structures of the described refractive correctors canbe applied to existing refracting structures such as contact lenses orIOLs with base power, or by direct writing into the human cornea usingrecently developed blue-femtosecond laser high repetition ratetechnology (see, e.g., “First Demonstration of Ocular Refractive ChangeUsing Blue-IRIS in Live Cats,” Investigative Ophthalmology and VisualScience, July 2014, Vol. 55:4603-4612, and U.S. Pat. Nos. 8,617,147,8,486,055 and 8,512,320, the disclosures of which are incorporatedherein by reference in their entireties), and further laser writingprocesses such as described in U.S. Pat. Nos. 6,450,642, 7,105,110, US2008/0001320, US 2009/0287306, US 2009/0157178, US 2010/0228345, US2012/0310340, and US 2012/0310223 referenced above, the disclosures ofwhich are further incorporated herein by reference in their entireties.Alternatively, the described mixed continuous and discontinuousrefractive corrector structures may be made by conventional molding orlathing and milling processes. Mixed continuous-discontinuousFresnel-type lenses of the kinds described in this disclosure may findapplications outside the field of ophthalmology as well.

In particular embodiments, the wavefront cross-section phase profile inthe central zone and peripheral region of the refractive corrector isestablished at least in part by laser machining the refractive corrector(or by direct writing into the human cornea) employing any of thelaser-writing techniques referenced above, as wavefront cross-sectionprofiles as described herein have the advantage of reducing the time towrite an equivalent totally continuous wavefront cross-section profilein a refractive corrector, while providing lower scatter and improvedvision correction in comparison to complete modulo-2π phase shiftprofiles written across the entire refractive corrector phase profile.More particularly, it is especially advantageous when laser writing awavefront cross-section profile to vary the refractive index of thematerials forming at least one of such central zone and peripheralregion across at least one of such central zone and peripheral region,and further when laser writing a wavefront cross-section phase profileto vary the refractive index of the materials forming each of suchcentral zone and peripheral region across each of such central zone andperipheral region.

In particular embodiments, the refractive corrector wavefrontcross-section profile may be formed by irradiating an optical, polymericmaterial, or by direct writing into the human cornea, with very shortlaser pulses of light as described in U.S. Publication Nos.2008/0001320, 2009/0287306, 2012/0310340 and 2012/0310223 incorporatedby reference above, where such short laser pulses are of sufficientenergy such that the intensity of light within the focal volume willcause a nonlinear absorption of photons (typically multi-photonabsorption) and lead to a change in the refractive index of the materialwithin the focal volume, while the material just outside of the focalvolume will be minimally affected by the laser light. The femtosecondlaser pulse sequence pertaining to an illustrative embodiment, e.g.,operates at a high repetition-rate, e.g., 80 MHz, and consequently thethermal diffusion time (>0.1p) is much longer than the time intervalbetween adjacent laser pulses (˜11 ns). Under such conditions, absorbedlaser energy can accumulate within the focal volume and increase thelocal temperature. This thermal mechanism likely plays a role in theformation of laser-induced refractive structures in optical, polymericmaterials. Moreover, the presence of water in the polymeric material isbelieved to advantageously influence the formation of the refractivestructures. As such, optical hydrogel polymers provide much greaterprocessing flexibility in the formation of the refractive structures ascompared to zero or low water content optical polymers, e.g., thehydrophobic acrylates or low-water (1% to 5% water content) acrylatematerials. The irradiated regions exhibit little or no scattering loss,which means that the resulting refractive structures that form in thefocal volume are not clearly visible under appropriate magnificationwithout phase contrast enhancement. In other words, the refractivestructures are virtually transparent to the human eye without some formof image enhancement. An optical material is a polymeric material thatpermits the transmissions of at least 80% of visible light through thematerial, that is, an optical material does not appreciably scatter orblock visible light.

According to one specific embodiment, a refractive corrector is formedby providing an optical, polymeric lens material having an anteriorsurface and posterior surface and an optical axis intersecting thesurfaces; and forming at least one laser-modified layer disposed betweenthe anterior surface and the posterior surface with light pulses from alaser by scanning the light pulses along regions of the optical,polymeric material to cause changes in the refractive index of thepolymeric lens material, so that the optical, polymeric lens materialcomprises (a) a central zone having a continuous wavefront cross-sectionphase profile, having a wavefront maximum height of greater than 1design wavelength λ in the area of the central zone, and (b) aperipheral region comprising multiple segments and having adiscontinuous wavefront cross-section phase profile having phase shiftsbetween segments that are equal to the design wavelength or multiples ofthe design wavelength, wherein the phase shifts in the peripheral regionare less than or equal to the wavefront maximum height in the centralzone. In such embodiment, the at least one laser-modified layer forms atleast part of at least one of the central zone or the peripheral region.

According to another embodiment, a refractive property of ocular tissuein an eye is modified by forming at least one optically-modified layerin at least one of the corneal stroma and the crystalline lens oculartissue in an eye by scanning light pulses from a laser focused in thecorneal stroma or crystalline lens ocular tissue along regions of thecorneal stroma or crystalline lens ocular tissue to cause changes in therefractive index within the ocular tissue to form a modified cornealstroma or crystalline lens, so that the modified corneal stroma orcrystalline lens comprises (a) a central zone having a continuouswavefront cross-section phase profile, having a wavefront maximum heightof greater than 1 design wavelength λ in the area of the central zone,and (b) a peripheral region comprising multiple segments and having adiscontinuous wavefront cross-section phase profile having phase shiftsbetween segments that are equal to the design wavelength or multiples ofthe design wavelength, wherein the phase shifts in the peripheral regionare less than or equal to the wavefront maximum height in the centralzone. In such embodiment, the at least one optically-modified layerforms at least part of at least one of the central zone or theperipheral region.

Femtosecond laser pulse writing methods may be more advantageouslycarried out if an optical polymeric material, such as, e.g., an opticalhydrogel material, includes a photosensitizer, as more particularlytaught in U.S. Publication Nos. 2009/0287306 and 2012/0310340incorporated by reference above. The presence of the photosensitizerpermits one to set a scan rate to a value that is at least fifty timesgreater, or at least 100 times greater, than a scan rate without aphotosensitizer present in the material, and yet provide similarrefractive structures in terms of the observed change in refractiveindex of the material in the focal volume. Alternatively, thephotosensitizer in the polymeric material permits one to set an averagelaser power to a value that is at least two times less, moreparticularly up to four times less, than an average laser power withouta photosensitizer in the material, yet provide similar refractivestructures. A photosensitizer having a chromophore with a relativelylarge multi-photon absorption cross section is believed to capture thelight radiation (photons) with greater efficiency and then transfer thatenergy to the optical polymeric material within the focal volume. Thetransferred energy leads to the formation of the refractive structuresand the observed change in the refractive index of the material in thefocal volume.

A 60X 0.70NA Olympus LUCPlanFLN long-working-distance microscopeobjective with variable spherical aberration compensation may beemployed to laser-write refractive segments. As indicated by thefollowing equation

${\Delta {T\left( {r,z,{t = 0}} \right)}} = \frac{\beta {\tau_{P}\left\lbrack {I\left( {0,0} \right)} \right\rbrack}^{2}{\exp \left\lbrack {{- 4}\left( {\frac{r^{2}}{a^{2}} + \frac{z^{2}}{b^{2}}} \right)} \right\rbrack}}{c_{p}\rho}$

the localized instantaneous temperature depends on both the pulseintensity and the magnitude of the two-photon absorption (TPA)coefficient. In order to produce an optical modification of a materialthat is of purely refractive character, i.e., non-absorbing orscattering, it is important to avoid optical damage, i.e., observedburning (scorching) or carbonization of the polymeric material. Suchmaterial or optical damage can be caused by excitation intensitiesexceeding a critical free-electron density. For hydrogel polymerscontaining a fair amount of water, the optical breakdown threshold ismuch lower than that in silica glasses. This breakdown threshold limitsthe pulse energy (in many cases to approximately 0.1 nJ to 20 nJ) thatthe hydrogel polymers can tolerate, and yet provide the observed changesin the refractive index within the focal volume.

Another way to increase energy absorption at a given intensity level isto increase the nonlinear absorption coefficient β by doping theoptical, polymeric material with a particular chromophore and tuning theshort pulse laser near a two-photon transition of the chromophore. Inthis regard, optical, hydrogel materials doped with a non-polymerizablephotosensitizer or a polymerizable photosensitizer have been prepared.The photosensitizer will include a chromophore having a two-photon,absorption cross-section of at least 10 GM between a laser wavelengthrange of 750 nm to 1100 nm. In the former case of a non-polymerizablephotosensitizer, solutions containing a photosensitizer may be preparedand the optical, hydrogel polymeric materials may be allowed to come incontact with such solutions to allow up-take of the photosensitizer intothe polymeric matrix of the polymer. In the later case of apolymerizable photosensitizer, monomers containing a chromophore, e.g.,a fluorescein-based monomer, may be used in the monomer mixture used toform the optical, polymeric material such that the chromophore becomespart of the polymeric matrix. Further, one could easily use a solutioncontaining a non-polymerizable photosensitizer to dope an optical,polymeric material that had been prepared with a polymerizablephotosensitizer. Also, it is to be understood that the chromophoricentities could be the same or different in each respectivephotosensitizer.

The concentration of a polymerizable, monomeric photosensitizer having atwo-photon, chromophore in an optical material, preferably an optical,hydrogel material, can be as low as 0.05 wt. % and as high as 10 wt. %.Exemplary concentration ranges of polymerizable monomer having atwo-photon, chromophore in an optical, hydrogel material is from 0.1 wt.% to 6 wt. %, 0.1 wt. % to 4 wt. %, and 0.2 wt. % to 3 wt. %. In variousaspects, the concentration range of polymerizable monomerphotosensitizer having a two-photon, chromophore in an optical, hydrogelmaterial is from 0.4 wt. % to 2.5 wt. %.

Due to the high repetition rate pulse sequence used in the irradiationprocess, the accumulated focal temperature increase can be much largerthan the temperature increase induced by a single laser pulse. Theaccumulated temperature increases until the absorbed power and thedissipated power are in dynamic balance. For hydrogel polymers,thermal-induced additional crosslinking within the polymer network canproduce a change in the refractive index as the local temperatureexceeds a transition temperature. If the temperature increase exceeds asecond threshold, a somewhat higher temperature than the transitiontemperature, the polymer is pyrolytically degraded and carbonizedresidue and water bubbles are observed. In other words, the materialexhibits visible optical damage (scorching). Each of the followingexperimental parameters such as laser repetition rate, laser wavelengthand pulse energy, TPA coefficient, and water concentration of thematerials should be considered so that a desired change in therefractive index can be induced in the hydrogel polymers without opticaldamage.

The pulse energy and the average power of the laser, and the rate atwhich the irradiated regions are scanned, will in-part depend on thetype of polymeric material that is being irradiated, how much of achange in refractive index is desired and the type of refractivestructures one wants to create within the material. The selected pulseenergy will also depend upon the scan rate and the average power of thelaser at which the refractive structures are written into the polymermaterial. Typically, greater pulse energies will be needed for greaterscan rates and lower laser power. For example, some materials will callfor a pulse energy from 0.05 nJ to 100 nJ or from 0.2 nJ to 10 nJ.

Within the stated pulse energies above, the optical, hydrogel polymericmaterial may be irradiated at a scan rate of, e.g., at least 0.1 mm/s,from 0.1 min/s to 10 mm/s or from 0.4 mm/s to 4 mm/s.

Within the stated pulse energies and scan rates above, the average laserpower used in the irradiation process may be, e.g., from 10 mW to 400mW, or from 40 mW to 220 mW.

In one embodiment, the average pulse energy may be from 0.2 nJ to 10 nJand the average laser power may be from 40 mW to 220 mW. The laser alsooperates within a wavelength of 650 nm to 950 nm. Within the statedlaser operating powers, the optical, hydrogel polymeric material isirradiated at a scan rate, e.g., of from 0.4 mm/s to 4 mm/s.

A photosensitizer will include a chromophore in which there is little orno intrinsic linear absorption in the spectral range of 600-1000 nm. Thephotosensitizer is present in the optical, hydrogel polymeric materialto enhance the photoefficiency of the two-photon absorption required forthe formation of the described refractive structures. Photosensitizersof particular interest include, but are not limited to, the followingcompounds. The compounds below are merely exemplary.

As described in U.S. Publication Nos. 2009/0287306 and 2012/0310340 ingreater detail in the Example sections, a commercial IOL material,Akreos®, presently marketed by Bausch & Lomb, was subjected to laserirradiation according to the processes described therein. An Akreos® IOLis a HEMA-based, hydrogel material with 26% to 28% water content. Themicromachining process was used to imprint refractive structures in anAkreos® IOL without photosensitizer and an Akreos® IOL doped with asolution containing 17 wt. % coumarin-1. The irradiation experimentswere conducted with both dry and hydrated materials. The refractivestructures formed only in the hydrated materials. In brief, themagnitude of the measured change in refractive index was at least tentimes greater in the Akreos® IOL doped with the coumarin solution at agiven scan rate and an average laser power than the Akreos® IOL withoutthe coumarin.

In another illustrative aspect described in U.S. Publication Nos.2009/0287306 and 2012/0310340, a balafilcon A silicone hydrogel wasprepared by adding fluorescein monomer (0.17% by weight) as apolymerizable photosensitizer to the polymer monomer mixture. Thebalafilcon A doped with fluorescein was then subjected to laserradiation according to the processes described therein. Again, thedescribed irradiation process was used to imprint refractive structuresin the silicone hydrogel without photosensitizer and the siliconehydrogel doped with 0.17 wt. % fluorescein monomer. Again, experimentswere conducted with both dry and hydrated materials, and again, therefractive structures formed only in the hydrated materials. In brief,the magnitude of the measured change in refractive index was at leastten times greater in the balafilcon A silicone hydrogel doped with 0.17wt. % fluorescein monomer at an average laser power of 60 mW thanbalafilcon A without the photosensitizer. This 10-fold difference inchange in refractive index was observed even with a 10-fold increase inscan rate in the photosensitized material; i.e., 0.5 mm/s in the undopedmaterial and 5.0 mm/s in the photosensitized material.

The laser may generate light with a wavelength in the range from violetto near-infrared. In various aspects, the wavelength of the laser may bein the range from 400 nm to 1500 nm, from 400 nm to 1200 nm, or from 650nm to 950 nm.

In an exemplary aspect, the laser may be a pumped Ti:sapphire laser withan average power of 10 mW to 1000 mW. Such a laser system will generatelight with a wavelength of approximately 800 nm. In another exemplaryaspect, an amplified fiber laser that can generate light with awavelength from 1000 nm to 1600 nm may be used.

The laser may have a peak intensity at focus of greater than 10¹³ W/cm².At times, it may be advantageous to provide a laser with a peakintensity at focus of greater than 10¹⁴ W/cm², or greater than 10¹⁵W/cm².

The ability to form refractive structures in optical polymeric materialsprovides an important opportunity to an ophthalmic surgeon orpractitioner to modify the refractive index of an optical device, e.g.,an intraocular lens or corneal inlay, following implantation of thedevice into an eye of a patient. The method allows the surgeon tocorrect aberrations as a result of the surgery. The method also allowsthe surgeon to adjust the refractive properties of the lens or inlay byadjusting the refractive index in the irradiated regions based on thevision correction required of each patient. For example, starting from alens of selected power (will vary according to the ocular requirementsof the patient), the surgeon can further adjust the refractiveproperties of the lens to correct a patient's vision based upon theindividual needs of the patient. In essence, an intraocular lens wouldessentially function like a contact lens or glasses to individuallycorrect for the refractive error of a patient's eye. Moreover, becausethe implanted lens can be adjusted by adjusting the refractive index ofselect regions of the lens, post-operative refractive errors resultingfrom pre-operative measurement errors, variable lens positioning duringimplantation, and wound healing (aberrations) can be corrected or finetuned in-situ.

Typically, the irradiated portions of the optical, hydrogel polymericmaterial will exhibit a positive change in refractive index of about0.01 or more. In one embodiment, the refractive index of the region willincrease by about 0.03 or more. As disclosed in U.S. Publication Nos.2009/0287306 and 2012/0310340, a positive change in refractive index ina hydrated, Akreos® IOL material of about 0.06 has been measured.

In an exemplary aspect, the irradiated regions of an optical, polymericmaterial can be defined by two- or three-dimensional structuresproviding the desired wavefront cross-section profile. The two- orthree-dimensional structures can comprise an array of discretecylinders, a series of lines, or a combination of an array of cylindersand a series of lines. Moreover, the two- or three-dimensionalstructures can comprise area or volume filled structures, respectively.These area or volume filled structures can be formed by continuouslyscanning the laser at a constant or varying scan rate over a selectedregion of the polymeric material. Nanometer-sized structures can also beformed by the zone-plate-array lithography method describe by R. Menonet al., Proc. SPIE, Vol. 5751, 330-339 (May 2005); Materials Today, p.26 (February 2005).

In one aspect, the refractive structures may be formed proximate to thetop anterior surface of an intraocular lens. For example, a positive ornegative lens element (three-dimensional) is formed within a 300 μmvolume, or within a 100 μm volume, from the anterior surface of thelens. The term “anterior surface” is the surface of the lens that facesthe anterior chamber of a human eye.

A non-limiting embodiment of a laser system 10 which may be used forirradiating an optical, polymeric material with a laser to modify therefractive index of the material in select regions to form a refractivecorrector having a wavefront cross-section phase profile as describedherein is illustrated in FIG. 2. A laser source comprises a Kerr-lensmode-locked Ti:Sapphire laser 12 (Kapteyn-Murnane Labs, Boulder, Colo.)pumped by 4 W of a frequency-doubled Nd:YVO4 laser 14. The lasergenerates pulses of 300 mW average power, 30 fs pulse width, and 93 MHzrepetition rate at wavelength of 800 nm. Because there is a reflectivepower loss from the mirrors and prisms in the optical path, and inparticular from the power loss of the objective 20, the measured averagelaser power at the objective focus on the material is about 120 mW,which indicates the pulse energy for the femtosecond laser is about 1.3nJ.

Due to the limited laser pulse energy at the objective focus, the pulsewidth must be preserved so that the pulse peak power is strong enough toexceed the nonlinear absorption threshold of the materials. Because alarge amount of glass inside the focusing objective significantlyincreases the pulse width due to the positive dispersion inside of theglass, an extra-cavity compensation scheme is used to provide thenegative dispersion that compensates for the positive dispersionintroduced by the focusing objective. Two SF10 prisms 24 and 28 and oneending mirror 32 form a two-pass, one-prism-pair configuration. In aparticular instance, a 37.5 cm separation distance between the prisms isused to compensate for the positive dispersion of the microscopeobjective and other optics within the optical path.

A collinear autocorrelator 40 using third-order harmonic generation isused to measure the pulse width at the objective focus. Both 2^(nd) and3^(rd) harmonic generation have been used in autocorrelationmeasurements for low NA or high NA objectives. Third-order surfaceharmonic generation (THG) autocorrelation may be used to characterizethe pulse width at the focus of the high-numerical aperture (NA)objectives because of its simplicity, high signal to noise ratio, andlack of material dispersion that second harmonic generation (SHG)crystals usually introduce. The THG signal is generated at the interfaceof air and an ordinary cover slip 42 (Corning No. 0211 Zinc Titaniaglass), and measured with a photomultiplier 44 and a lock-in amplifier46. After using a set of different high-numerical-aperture objectivesand carefully adjusting the separation distance between the two prismsand the amount of glass inserted, a transform-limited 27 fs durationpulse is used, which is focused by a 60X 0.70NA Olympus LUCPlanFLNlong-working-distance objective 48.

Because the laser beam will spatially diverge after it comes out of thelaser, a concave mirror pair 50 and 52 is added into the optical path inorder to adjust the dimension of the laser beam so that the laser beamcan optimally fill the objective aperture. A 3D 100 nm resolution DCservo motor stage 54 (Newport VP-25XA linear stage) and a 2D 0.7 nmresolution piezo nanopositioning stage (PI P-622.2CD piezo stage) arecontrolled and programmed by a computer 56 as a scanning platform tosupport and locate the samples. The servo stages have a DC servo-motorso they can move smoothly between adjacent steps. An optical shuttercontrolled by the computer with 1 ms time resolution is installed in thesystem to precisely control the laser exposure time. With customizedcomputer programs, the optical shutter could be operated with thescanning stages to micromachine different patterns in the materialsusing different scanning speeds at different position or depth in theoptical material, and different laser exposure times. In addition, a CCDcamera 58 along with a monitor 62 is used beside the objective 20 tomonitor the process in real time.

The method and optical apparatus described above can be used to modifythe refractive index of an intraocular lens following the surgicalimplantation of the intraocular lens in a human eye (or before the lensis implanted in an eye).

Accordingly, an embodiment described herein is directed to a methodcomprising identifying and measuring the aberrations resulting from thesurgical procedure of providing a patient with an IOL. Once theaberrations are identified and quantified using methods well known inthe art of ophthalmology, this information is processed by a computer.Of course, information related to the requisite vision correction foreach patient can also be identified and determined, and this informationcan also be processed by a computer. There are a number of commerciallyavailable diagnostic systems that are used to measure the aberrations.For example, common wavefront sensors used today are based on theSchemers disk, the Shack Hartmann wavefront sensor, the Hartmann screen,and the Fizeau, and Twyman-Green interferometers. The Shack-Hartmannwavefront measurement system is known in the art and is describedin-part by U.S. Pat. Nos. 5,849,006; 6,261,220; 6,271,914 and 6,270,221.Such systems operate by illuminating a retina of the eye and measuringthe reflected wavefront.

Once the aberrations are identified and quantified, the computerprograms determine the position and shape of the refractive structuresto be written into the lens material to correct for those aberrations orto provide vision correction to the patient. These computer programs arewell known to those of ordinary skill in the art. The computer thencommunicates with the laser-optical system and select regions of thelens are irradiated with a laser having a pulse energy from 0.05 nJ to1000 nJ as described herein, to provide a wavefront cross-section phaseprofile comprising a central zone and peripheral region in accordancewith the present invention.

The optical, hydrogel polymeric materials that can be irradiated with alaser according to the methods described to form refractive correctorsin accordance with various embodiments can be any optical, hydrogelpolymeric material known to those of ordinary skill in the polymericlens art, particularly those in the art familiar with optical polymericmaterials used to make intraocular lenses. Non-limiting examples of suchmaterials include those used in the manufacture of ophthalmic devices,such as siloxy-containing polymers, acrylic, hydrophilic or hydrophobicpolymers or copolymers thereof. The forming of the refractive structuresis particularly suited for modifying the refractive index in select anddistinct regions of a polymeric, optical silicone hydrogel, or apolymeric, optical non-silicone hydrogel.

The term “hydrogel” refers to an optical, polymeric material that canabsorb greater than 10% by weight water based on the total hydratedweight. In fact, many of the optical, hydrogel polymeric materials willhave a water content greater than 15% or greater than 20%. For example,many of the optical, hydrogel polymeric materials will have a watercontent from 15% to 60% or from 15% to 40%.

The optical, hydrogel polymeric materials are of sufficient opticalclarity, and will have a relatively high refractive index ofapproximately 1.40 or greater, particularly 1.48 or greater. Many ofthese materials are also characterized by a relatively high elongationof approximately 80 percent or greater.

In one embodiment, the optical polymeric materials are prepared as acopolymer from at least three monomeric components. The first monomericcomponent, preferably a monomeric component with aromatic functionality,is present in the copolymer in an amount of at least 60% by weight, andits homopolymer will have a refractive index of at least 1.50,particularly at least 1.52 or at least 1.54. The second monomericcomponent, preferably, an alkyl(meth)acrylate, is present in thecopolymer in an amount from 3% to 20% or from 3% to 10%, by weight. Thefirst and second monomeric components together represent at least 70% byweight of the copolymer. The term “homopolymer” refers to a polymer thatis derived substantially completely from the respective monomericcomponent. Minor amounts of catalysts, initiators, and the like can beincluded, as is conventionally the case, in order to facilitate theformation of the homopolymer.

Particularly useful first monomeric components include styrene, vinylcarbazole, vinyl naphthalene, benzyl(meth)acrylate,phenyl(meth)acrylate, naphthyl(meth)acrylate,2-phenoxyethyl(meth)acrylate, 2,3-dibromopropyl-(meth)acrylate and anyone mixture thereof. Particularly useful second monomeric componentsinclude n-butyl(meth)acrylate, n-hexyl(meth)acrylate,2-ethylhexyl-(meth)acrylate, 2-ethoxyethyl(meth)acrylate,2,3-dibromopropyl(meth)acrylate, 1,1-dihydroperfluorobutyl(meth)acrylateand any one mixture thereof.

The third monomeric component is a hydrophilic monomeric component. Thehydrophilic component is present in an amount, from 2% to 30% by weightof the copolymer. The hydrophilic component is particularly present inan amount of less than about 20% by weight of the copolymer. Copolymersthat include about 10% by weight or more of a hydrophilic monomericcomponent tend to form hydrogels if placed in an aqueous environment.The term “hydrophilic monomeric component” refers to compounds thatproduce hydrogel-forming homopolymers, that is, homopolymers whichbecome associated with at least 25% of water, based on the weight of thehomopolymer, if placed in contact with an aqueous solution.

Specific examples of useful hydrophilic monomeric components includeN-vinyl pyrrolidone; hydroxyalkyl (meth)acrylates such as 2-hydroxyethyl(meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl(meth)acrylate, 4-hydroxybutyl (meth)acrylate, 2,3-dihydroxypropyl(meth)acrylate and the like; acrylamide; N-alkyl acrylamides such asN-methyl acrylamide, N-ethyl acrylamide, N-propyl acrylamide, N-butylacrylamide and the like; acrylic acid; methacrylic acid; and the likeand any one mixture thereof.

In another embodiment, the optical polymeric materials are prepared as acopolymer from at least two monomeric components and a photosensitizer.The photosensitizer can be polymerizable or be entrapped within theformed polymer. The first monomeric component is a hydrophilic monomericcomponent. The hydrophilic component is present in an amount from 50% to90% by weight of the copolymer. The hydrophilic component isparticularly present in an amount of 60% to 85% by weight of thecopolymer. The second monomeric component, preferably, analkyl(meth)acrylate, is present in the copolymer in an amount from 5% to20% or from 3% to 10%, by weight. The first and second monomericcomponents together represent at least 90% by weight of the copolymer.

The polymeric optical materials will likely include a crosslinkcomponent that can form crosslinks with at least the first or the secondmonomeric components. Advantageously, the crosslink component ismulti-functional and can chemically react with both the first and secondmonomeric components. The crosslink component is often present in aminor amount relative to the amounts of the first and second monomericcomponents. Particularly, the crosslink component is present in acopolymer in an amount of less than about 1% by weight of the copolymer.Examples of useful crosslink components include ethylene glycoldimethacrylate, propylene glycol dimethacrylate, ethylene glycoldiacrylate and the like and mixtures thereof.

In one aspect, the optical, polymeric materials can be prepared from oneor more aromatic (meth)acrylate monomers having the formula:

wherein: R is H or CH₃; m is an integer selected from 0 to 10; Y isnothing, 0, S, or NR¹, wherein R¹ is H, CH₃, C₂-C₆ alkyl, iso-OC₃H₇,phenyl or benzyl; Ar is any aromatic ring, e.g., phenyl, which can beunsubstituted or substituted with H, CH₃, C₂H₅, n-C₃H₇, iso-C₃H₇, OCH₃,C₆H₁₁, Cl, Br, phenyl or benzyl; and a crosslinking component.

Exemplary aromatic (meth)acrylate monomers include, but are not limitedto: 2-ethylphenoxy (meth)acrylate, 2-ethylthiophenyl (meth)acrylate,2-ethylaminophenyl (meth)acrylate, phenyl-(meth)acrylate, benzyl(meth)acrylate, 2-phenylethyl (meth)acrylate,3-phenylpropyl-(meth)acrylate, 4-phenylbutyl (meth)acrylate,4-methylphenyl (meth)acrylate, 4-methylbenzyl (meth)acrylate,2-2-methylphenylethyl (meth)acrylate, 2-3-methylphenylethyl(meth)acrylate, 2-4-methylphenylethyl (meth)acrylate,2-(4-propylphenyl)ethyl (meth)acrylate, 2-(4-(1-methylethyl)phenyl)ethylmethacrylate, 2-(4-methoxyphenyl)ethyl methacrylate and the like.

Generally, if the optical, polymeric material is prepared with both anaromatic acrylate and an aromatic methacrylate as defined by the formulaabove, the materials will generally comprise a greater mole percent ofaryl acrylate ester residues than of aryl methacrylate ester residues.It is preferred that the aryl acrylate monomers constitute from about 20mole percent to about 60 mole percent of the polymer, while the arylmethacrylate monomers constitute from about 5 mole percent to about 20mole percent of the polymer. Most advantageous is a polymer comprisingabout 30-40 mole percent 2-phenylethyl acrylate and about 10-20 molepercent 2-phenylethyl methacrylate. Hydrophilic monomer is also presentin about 20-40 mol percent.

In another aspect, the optical, polymeric materials will have a fullyhydrated (equilibrium) water content from 5% to 15% by weight, whichalso helps to minimize the degree of hazing following thermal stress asdescribed, as well as minimize the formation of water vacuoles in-vivo.To achieve the desired water content, one may include a hydrophilic,aromatic monomer having a formula, G-D-Ar, wherein Ar is a C₆-C₁₄aromatic group having a hydrophilic substituent, in the polymerizablecompositions. D is a divalent linking group, and G is a polymerizableethylenic site.

One particular hydrophilic aromatic monomer is represented by theformula

wherein R is hydrogen or CH₃; D is a divalent group selected from thegroup consisting of straight or branched C₁-C₁₀ hydrocarbons and analkyleneoxide (e.g., —(CH₂CH₂O)_(n)—), and E is selected from the groupconsisting of hydrogen (if D is alkyleneoxide), carboxy, carboxamide,and monohydric and polyhydric alcohol substituents. Exemplaryhydrophilic substituents include, but are not limited to, —COOH,—CH₂—CH₂OH, —(CHOH)₂CH₂OH, —CH₂—CHOH—CH₂OH, poly(alkylene glycol),—C(O)O—NH₂ and —C(O)—N(CH₃)₂.

Exemplary hydrophilic, aromatic monomers are represented by thefollowing

wherein R is hydrogen or CH₃ and R¹ is —C(O)O—NH₂ or —C(O)—N(CH₃)₂.

In another aspect, the optical, polymeric material is prepared from afirst aromatic monomeric component, which is present in 5-25% by weight,the second monomeric component is a hydrophilic monomeric component,e.g., 2-hydroxyethyl (meth)acrylate, which is present from 30 to 70% byweight; and 5 to 45% by weight of a another alkyl (meth)acrylateselected from the group consisting of methyl (meth)acrylate, ethyl(meth)acrylate, propyl (meth)acrylate, butyl (meth)acrylate, pentyl(meth)acrylate, hexyl meth)acrylate, heptyl (meth)acrylate, nonyl(meth)acrylate, stearyl meth)acrylate, octyl (meth)acrylate, decyl(meth)acrylate, lauryl (meth)acrylate, pentadecyl (meth)acrylate and2-ethylhexyl (meth)acrylate. Among the alkyl (meth)acrylates, thosecontaining 1 to 3 carbon atoms of alkyl group are particularlyadvantageous.

Exemplary aromatic monomeric components include ethylene glycol phenylether acrylate (EGPEA), poly(ethylene glycol phenyl ether acrylate)(polyEGPEA), phenyl methacrylate, 2-ethylphenoxy methacrylate,2-ethylphenoxy acrylate, hexylphenoxy methacrylate, hexylphenoxyacrylate, benzyl methacrylate, 2-phenylethyl methacrylate,4-methylphenyl methacrylate, 4-methylbenzyl methacrylate,2-2-methyphenylethyl methacrylate, 2-3-methylphenylethyl methacrylate,2-4-methylphenylethyl methacrylate, 2-(4-propylphenyl)ethylmethacrylate, 2-(4-(1-methylethyl)pheny)ethyl methacrylate,2-(4-methoxyphenyl)ethylmethacrylate, 2-(4-cyclohexylpheny)ethylmethacrylate, 2-(2-chlorophenyl)ethyl methacrylate,2-(3-chlorophenyl)ethyl methacrylate, 2-(4-chlorophenyl)ethylmethacrylate, 2-(4-bromophenyl)ethyl methacrylate,2-(3-phenylphenyl)ethyl methacrylate, 2-(4-phenylphenyl)ethylmethacrylate), 2-(4-benzylphenyl)ethyl methacrylate, and the like,including the corresponding methacrylates and acrylates, and includingmixtures thereof. EGPEA and polyEGPEA are two of the more preferredfirst monomeric components.

In another aspect, the optical, polymeric material is prepared from ahydrophilic acrylic that comprises about 90% (by weight)N-vinylpyrrolidone (NVP) and about 10% (by weight)4-t-butyl-2-hydroxycyclohexyl methacrylate. This methacrylate hydrogelcan absorb about 80% (by weight) water because of the high percentage ofNVP. Its refractive index when hydrated is very close to the index ofwater. Another hydrophilic acrylic of interest is referred to as HEMA B,which is a poly(2-hydroxyethyl methacrylate) cross-linked with about0.9% (by weight) of ethylene glycol dimethacrylate (“EGDMA”). ThisHEMA-hydrogel can absorb about 37% (by weight) water.

One particular hydrophilic, acrylic material of interest is based upon acommercially available IOL sold in the market by Bausch & Lomb under thetrade name Akreos®. This acrylic material comprises about 80% by weightHEMA and 20 wt % MMA.

The optical, polymeric material can also be prepared by copolymerizing aspecific monomer mixture comprising perfluorooctylethyloxypropylene(meth)acrylate, 2-phenylethyl (meth)acrylate, an alkyl (meth)acrylatemonomer having the following general formula,

wherein R is hydrogen or methyl and R¹ is a linear or branched C₄-C₁₂alkyl group, hydrophilic monomer and a crosslinking monomer. Anexemplary list of alkyl (meth)acrylate monomer include n-butyl acrylate,isobutyl acrylate, isoamyl acrylate, hexyl acrylate, 2-ethylhexylacrylate, octyl acrylate, isooctyl acrylate, decyl acrylate, isodecylacrylate, and the like.

The perfluorooctylethyloxypropylene (meth)acrylate is present from 5% to20% by weight, the 2-phenylethyl (meth)acrylate is present from 20% to40% by weight, the alkyl (meth)acrylate monomer is present from 20% to40% by weight, the hydrophilic monomer is present from 20% to 35%, andthe crosslinking agent is present from 0.5% to 2% by weight.

The optical, polymeric component will likely include a crosslinkingagent. The copolymerizable crosslinking agent(s) useful in forming thecopolymeric material include any terminally ethylenically unsaturatedcompound having more than one unsaturated group. Particularly, thecrosslinking agent includes a diacrylate or a dimethacrylate. Thecrosslinking agent may also include compounds having at least two(meth)acrylate and/or vinyl groups. Particularly advantageouscrosslinking agents include diacrylate compounds.

The optical, polymeric materials are prepared by generally conventionalpolymerization methods from the respective monomeric components. Apolymerization mixture of the monomers in the selected amounts isprepared and a conventional thermal free-radical initiator is added. Themixture is introduced into a mold of suitable shape to form the opticalmaterial and the polymerization initiated by gentle heating. Typicalthermal, free radical initiators include peroxides, such as benzophenoneperoxide, peroxycarbonates, such as bis-(4-t-butylcyclohexyl)peroxydicarbonate, azonitriles, such as azobisisobytyronitrile, and thelike. A particular initiator is bis-(4-t-butylcyclohexyl)peroxydicarbonate (PERK). Alternatively, the monomers can bephotopolymerized by using a mold which is transparent to actinicradiation of a wavelength capable of initiating polymerization of theseacrylic monomers by itself. Conventional photoinitiator compounds, e.g.,a benzophenone-type photoinitiator, can also be introduced to facilitatethe polymerization.

Without exclusion as to any lens materials or material modifications,e.g., the inclusion of a photosensitizer, or laser parameters describedherein above, the foregoing disclosed techniques and apparatus can beused to modify the refractive properties, and thus, the dioptric power,of an optical polymeric material, typically, an optical hydrogelmaterial, in the form of, but not limited to, an IOL or corneal inlay,by creating (or machining) a refractive structure with a gradient indexin one, two or three dimensions of the optical material, as more fullydescribed in U.S. Publication Nos. 2012/0310340 and 2012/0310223,incorporated by reference above. The gradient refractive structure canbe formed by continuously scanning a continuous stream of femtosecondlaser pulses having a controlled focal volume in and along at least onecontinuous segment (scan line) in the optical material while varying thescan speed and/or the average laser power, which creates a gradientrefractive index in the polymer along the segment. Accordingly, ratherthan creating discrete, individual, or even grouped or clustered,adjoining segments of refractive structures with a constant change inthe index of refraction in the material, a gradient refractive index iscreated within the refractive structure, and thereby in the opticalmaterial, by continuously scanning a continuous stream of pulses. Asdescribed in greater detail in U.S. Publication No. 2012/0310340, sincethe refractive modification in the material arises from a multiphotonabsorption process, a well-controlled focal volume corrected forspherical (and other) aberrations will produce a segment havingconsistent and, if desired, constant depth over the length of the scan.As further noted, when a tightly focused laser beam consisting offemtosecond pulses at high repetition rate impinges on a material thatis nominally transparent at the incident laser wavelength, there islittle if any effect on the material away from the focal region. In thefocal region, however, the intensity can exceed one terawatt per squarecentimeter, and the possibility of absorbing two or more photonssimultaneously can become significant. In particular, the amount oftwo-photon absorption can be adjusted by doping or otherwise includingin the irradiated material with selected chromophores that exhibit largetwo-photon absorption cross-section at the proper wavelength (e.g.,between 750 nm and 1100 nm), which can significantly increase thescanning speed as already described. Also, multiple segments can bewritten into the material in a layer using different scan speeds and/ordifferent average laser power levels for various segments to create agradient index profile across the layer, i.e., transverse to the scandirection. Further, multiple, spaced gradient index (GRIN) layers can bewritten into the material along the z-direction (i.e., generally thelight propagation direction through the material) to provide a desiredrefractive change in the material that corrects for some, most, or allhigher order aberrations of a patient's eye. Such abilities to writecontinuously varying gradient index layers are particularly advantageousin forming refractive correctors having wavefront cross-section profilesin accordance with embodiments of the present invention. For ophthalmicapplications, it is of particular interest that GRIN refractivestructures are low scattering (as discussed above) and are of highoptical quality.

In an illustrative aspect disclosed in U.S. Publication No.2012/0310340, a cylindrical lens structure with a one-dimensionalquadratic gradient index was written in an optical, polymeric materialwith three GRIN layers each 5 μm thick, spaced by 10 μm in thez-direction (i.e., a layer of non-modified optical material having athickness of about 5 μm to 7 μm was between each two adjacent GRINlayers). The resulting cylindrical lens was designed to provideapproximately 1 diopter of astigmatism uniform along the length of thedevice.

As further disclosed in U.S. publication No. 2012/0310223, incorporatedby reference above, the femtosecond micromachining approach employedwith hydrogel materials may be adapted to similarly carry out refractivecorrection in biological tissues by reducing the femtosecond laser pulseenergies below the optical breakdown thresholds for such biologicaltissues, and gradient index layers may similarly be formed in suchbiological tissues by varying the scan rates and/or scan powers whilemaintaining pulse energies below such threshold energies. Moreparticularly, refractive structures may be formed in a living eye by amethod including (a) directing and focusing femtosecond laser pulses inthe blue spectral region within a cornea or a lens of the living eye atan intensity high enough to change the refractive index of the cornea orlens within a focal region, but not high enough to damage the cornea orlens or to affect cornea or lens tissue outside of the focal region; and(b) scanning the laser pulses across a volume of the cornea or the lensto provide the focal region with refractive structures in the cornea orthe lens. The refractive structures advantageously exhibit little or noscattering loss, which means that the structures are not clearly visibleunder appropriate magnification without contrast enhancement.

FIG. 3 shows a schematic representation of a refractive corrector in theform of a lens 100 having a central continuous refractive zone 120, anda peripheral Fresnel-type discontinuous phase shifting region 140. Asshown in FIG. 3, the peripheral region may circumscribe the centralzone, and more specifically an outer perimeter of the central zone andan outer perimeter of the peripheral region may be circular, where theoptical axis of the lens is at the center of the circular regions. Lens100 acts like a conventional refracting lens in the central zone, and asa Fresnel-type refractor in the peripheral region. In certainembodiments, the central zone may have an outer diameter of at least 10,at least 20, at least 25, or at least 30% of the outer diameter of theperipheral region, e.g., from 10% to 90%, from 20% to 80%, from 25% to75%, or from 30% to 70% of the outer diameter of the peripheral region.Alternatively, in further embodiments, the central zone may comprise atleast 20, at least 30, or at least 40% of the total area of the centralzone and peripheral region combined, e.g., from 20% to 90%, from 30% to85%, or from 40% to 80% of the total area of the central zone andperipheral region combined. The various embodiments thus provide adegree of freedom allowing one to choose a ratio of continuousrefracting region to that of the discontinuous phase shift region, inorder to provide desired visual acuity under specified conditions whilestill enabling reduced write times. In some specific embodiments, e.g.,providing a central zone having an outer diameter of from 30% to 70% ofthe diameter of the peripheral region may provide optimal combinedresults. In certain embodiments, e.g., the central zone may have adiameter of from about 0.5 mm to about 5 mm, and the peripheral regionmay have an outer diameter of from about 3 mm to about 10 mm, while inother embodiments such diameters may be larger or smaller.

Example: Designs Incorporating a Parabolic Central Phase Shift Region

One particular design for a refractive corrector consists of a simpleparabolic phase shift. As an illustrative example, wavefrontcross-sections of (a) continuous, (b) hybrid continuous/Fresnel and (c)complete modulo 2π phase wrapped Fresnel designs are shown in FIGS. 4A,4B and 4C, respectively. As the number of discrete steps in thewavefront decreases, these types of lenses become essentiallyconventional refracting structures with mostly continuous parabolicphase. Ultimately, for a fully continuous profile, the time taken towrite such large peak phase shifts in the central zone may becomeprohibitive, thereby losing the advantage of the mixedcontinuous/Fresnel-type design.

Example: Retinal Image Quality of Mixed Continuous-Fresnel Type Lenses

Previously, the imaging quality of kinoform Fresnel lenses and chromaticeffects have been considered (“Kinoform Lenses,” J. A. Jordan, Jr., P.M. Hirsch, L. B. Lesem, and D. L. Van Rooy, /Vol. 9, No. 8/AppliedOptics 1887, (1970); “Binary Optics Technology: The Theory ofMulti-Level Diffractive Optical Elements,” G. J. Swanson, TechnicalReport 854, MIT Lincoln Laboratories (1989)). In the present case, weevaluate the effects of the mixed (or hybrid) continuous centralzone/discontinuous peripheral Fresnel refractive corrector designs onhuman vision and visual performance.

The average human eye suffers from a significant magnitude oflongitudinal chromatic aberration (“Chromatic dispersions of the ocularmedia of human eyes.” Atchison, David A., and George Smith. JOSA A 22.1:29-37 (2005)), approximately 2 diopters over the visible spectrum(400-700 nm). Polychromatic retinal image quality was calculated for arange of positive dioptric powers and degrees of mixed continuous andFresnel type phase profiles for simple parabolic phase shifts of thetype illustrated in FIGS. 4A-4C, and the results are shown in FIG. 5,for the illustrative example of a 6 mm pupil.

The number of zones (of 2π phase height) in a conventional modulo 2πphase wrapped Fresnel design depends on the radius of the optical zone(R), wavelength (2) and optical power in diopters (D) in accordance withthe following formula:

Number of Zones=ceiling[R ² *D/(2λ)]

The quantity “number of zones” is an integer, therefore we round up tothe nearest integer, hence the “ceiling” function in the equation above.This equation comes from the definition of the Fresnel Number, which isdefined as the number of zones with half a wave of phase, or π radians.Therefore, the Fresnel number is twice the number of zones in a Fresnellens.

In FIG. 5, N is the number of additional zones included in the centralcontinuous region, relative to the number of zones in a conventionalmodulo 2π phase wrapped Fresnel design for a given dioptric power for a6 mm lens. Therefore, for a pure Fresnel lens, N=0 because there arezero additional zones included in the central region. We normalize themin and max N values reported in FIG. 5 between 0 and 1, because thereis a different maximum N value for lenses of different powers, as thelarger the dioptric power of a lens, the more zones there are in aconventional Fresnel lens, and thus the higher the maximum N value. Bynormalizing N, the concept behind hybridization is easily communicatedfor all dioptric lens powers. Table I below, e.g., is an illustrativeexample showing the relationships between, N, normalized N, the radiusof the inner continuous zone and the % of continuous central area of theentire lens for the case of 1 Diopter over a 6 mm diameter optical zone.

TABLE I Lens Power = 1 D, 6 mm pupil diameter Outer Inner % PupilContinuous Continuous Normalized Radius Region Area of Max N N Lens Type[mm] Radius [mm] Aperture 0 0.00 Fresnel 3.0 1.0 12% 1 0.14 Hybrid 3.01.5 25% 2 0.29 Hybrid 3.0 1.8 37% 3 0.43 Hybrid 3.0 2.1 49% 4 0.57Hybrid 3.0 2.3 61% 5 0.71 Hybrid 3.0 2.6 74% 6 0.86 Hybrid 3.0 2.8 86% 71.00 Continuous 3.0 3.0 100% 

As shown in FIG. 5, retinal image quality is optimized for Fresnel andhybrid Fresnel-continuous phase correctors of between approximately 2and 4 diopters due to the compensatory dispersive properties ofdiffractive discontinuities in the wavefront aberration.

Retinal image quality in FIG. 5 was quantified by computing thepolychromatic Strehl ratio. The Strehl ratio is defined as the ratio ofthe maximum value of the test-case polychromatic point spread function(PSF_(poly)) divided by the aberration-free (i.e. diffraction-limited)PSF_(poly). PSF_(poly) is defined below, as the weighted sum ofmonochromatic point spread functions (PSF) with relative defocus (W(λ),shown below) defined by the longitudinal chromatic aberration of theeye)(C₂ ⁰).

${PS{F_{poly}\left( {x,y} \right)}} = {\frac{1}{a}{\sum\limits_{\lambda = {405\mspace{11mu} {nm}}}^{695\mspace{11mu} {nm}}{{V_{\lambda}(\lambda)}{{PSF}\left( {x,y,e^{i_{\lambda}^{2\pi}{\lbrack{W{(\lambda)}}\rbrack}}} \right)}}}}$${W(\lambda)} = {{{C_{2}^{0}(\lambda)} \cdot \sqrt{3}}\left( {{2\rho^{2}} - 1} \right)}$

The weighting-coefficients, V_(λ), of the sum are specified by the humaneye's spectral sensitivity, shown in FIG. 6A. The longitudinal chromaticaberration of the eye is plotted in FIG. 6B.

To estimate expected visual acuity with the lens designs, we used aretinal image quality metric (Image Convolution Metric) which is verywell correlated with high-contrast visual acuity (R²=0.82). The imageconvolution metric is described in detail elsewhere (“Modifiedmonovision with spherical aberration to improve presbyopic through-focusvisual performance.” Zheleznyak, Len, Ramkumar Sabesan, Je-Sun Oh, ScottMacRae, and Geunyoung Yoon. Investigative ophthalmology & visual science54, no. 5 (2013): 3157-3165; “Impact of pupil transmission apodizationon presbyopic through-focus visual performance with sphericalaberration.” Zheleznyak, Len, HaeWon Jung, and Geunyoung Yoon.Investigative ophthalmology & visual science 55, no. 1 (2014): 70-77).In brief, it convolves an image (such as a resolution target) with thepolychromatic point spread function described above. The correlationbetween the convolved image with an unaberrated reference image iscalculated. This value was then correlated with visual acuity datameasured in subjects using an adaptive optics vision simulator.

Example: Pupil-Independent Hybrid Lens Designs

In addition to mixed, or hybrid, Fresnel and continuous phase profileswhich are allocated per inner/outer regions of the optical zone (i.e.pupil), hybridization may be implemented throughout the pupil. This isachieved by increasing the phase-wrap wavefront height to multiples ofthe design wavelength (i.e. λ, 2λ, 3λ, etc.). By increasing theFresnel-lens step height, the number of discontinuities in the wavefrontis decreased, as shown in FIGS. 7B and 7C relative to FIG. 7A. Similarto the pupil-dependent designs, phase-correctors with larger numbers ofdiscrete wavefront steps contribute to the cancellation of the eye'snative longitudinal chromatic aberration. Further embodiments of theinvention may employ a lens wherein different degrees of hybridizationare implemented in the central continuous zone and the outerdiscontinuous region having phase heights in even-integer multiples of7π (e.g. 2π, 4π, 6π and so on).

FIG. 8 depicts predicted visual acuity for a range of dioptric powersfor simple continuous parabolic phase shifts and corresponding completemodulo phase wrapped Fresnel lens designs and hybrid continuous/Fresnellens designs of the type illustrated in FIGS. 7A-7C, where the Hybridline refers to results for designs with 10π (i.e., 5 waves of phaseheight) for each refractive zone. The simulation was done with a 6.5 mmpupil diameter in an aberration-free model eye.

As shown in FIG. 8, continuous (dot-dash line) lenses maintain aconstant visual acuity for both positive and negative dioptric powers.Alternatively, conventional modulo 2π phase wrapped Fresnel lenses(solid line) interact with polychromatic optical quality (and thusvisual performance) due to their dispersive property of a negative Abbenumber (−3.45). Therefore, Fresnel lenses improve visual acuity forpositive powers, whereas negative powers degrade visual acuity. Finally,hybrid lenses (dash line) fall between the continuous and Fresnel lensdesigns, maintaining most of the improvement seen for Fresnel lenses forpositive powers, and providing improved visual acuity relative to theFresnel lenses for negative powers.

Example: Other Lens Designs

In addition to simple parabolic phase shifters, the described concept ofmixed continuous central zone with discontinuous peripheral areas can beemployed for other phase profiles, such as, e.g., hyperbolic phaseprofiles, aspheric phase profiles, and free-form/arbitrary phaseprofiles. Hyperbolic phase profiles may be employed, e.g., for addingmultifocality, as well as other known uses. Aspheric phase profiles withspherical aberrations (4th order and higher), may be employed to extendthe depth of focus (“Subjective depth of field in presence of 4th-orderand 6th-order Zernike spherical aberration using adaptive opticstechnology,” Benard, Yohann, Norberto Lopez-Gil, and Richard Legras,Journal of Cataract & Refractive Surgery 36.12 (2010): 2129-2138). FIG.9 depicts a cross-section of a hybrid wavefront with defocus andspherical aberration. Free-form/arbitrary phase profiles may beemployed, e.g., to correct the native higher order aberration profilesof individuals.

It will be appreciated that variants of the above-disclosed embodimentsand other features and functions, or alternatives thereof, may becombined into many other different systems or applications. Variouspresently unforeseen or unanticipated alternatives, modifications,variations, or improvements therein may be subsequently made by thoseskilled in the art which are also intended to be encompassed by thefollowing claims.

1. A refractive corrector comprising: (a) a central zone having acontinuous wavefront cross-section phase profile, having a wavefrontmaximum height of greater than 1 design wavelength a, in the area of thecentral zone; and (b) a peripheral region comprising multiple segmentsand having a discontinuous wavefront cross-section phase profile havingphase shifts between segments that are equal to the design wavelength ormultiples of the design wavelength, and wherein the phase shifts in theperipheral region are less than or equal to the wavefront maximum heightin the central zone.
 2. The refractive corrector of claim 1, wherein thecentral zone has a phase height greater than the phase shifts in theperipheral region.
 3. The refractive corrector of claim 1, wherein theperipheral region has a Fresnel structure having a phase shift betweensegments equal to the design wavelength.
 4. The refractive corrector ofclaim 1, wherein the peripheral region circumscribes the central zone.5. The refractive corrector of claim 1, wherein an outer perimeter ofthe central zone and an outer perimeter of the peripheral region arecircular.
 6. The refractive corrector of claim 1, wherein an opticalsurface of the central zone is parabolic.
 7. The refractive corrector ofclaim 1, wherein an optical surface of the central zone is hyperbolic.8. The refractive corrector of claim 1, wherein an optical surface ofthe central zone is a freeform surface.
 9. The refractive corrector ofclaim 1, wherein an optical surface of the central zone is aspheric. 10.The refractive corrector of claim 1, wherein a diameter of the centralzone is from 20% to 90% of the outer diameter of the peripheral region.11. The refractive corrector of claim 1, wherein the central zone andthe peripheral region are located in a contact lens.
 12. The refractivecorrector of claim 1, wherein the central zone and the peripheral regionare located in an intra-ocular lens.
 13. The refractive corrector ofclaim 1, wherein the peripheral region has a phase profile sampled into2π phase discontinuities.
 14. The refractive corrector of claim 1,wherein at least one of the central zone or peripheral region comprisesmaterials of varying refractive index contributing to the wavefrontcross-section phase profile.
 15. The refractive corrector of claim 1,wherein the refractive corrector is mono-focal for the designwavelength.
 16. The refractive corrector of claim 1, wherein the designwavelength is a wavelength between 400 and 700 nm.
 17. The refractivecorrector of claim 1, wherein the design wavelength is 555 nm.
 18. Amethod of forming a refractive corrector comprising: providing anoptical, polymeric lens material having an anterior surface andposterior surface and an optical axis intersecting the surfaces; andforming at least one laser-modified layer disposed between the anteriorsurface and the posterior surface with light pulses from a laser byscanning the light pulses along regions of the optical, polymericmaterial to cause changes in the refractive index of the polymeric lensmaterial; wherein the optical, polymeric lens material comprises (a) acentral zone having a continuous wavefront cross-section phase profile,having a wavefront maximum height of greater than 1 design wavelength λin the area of the central zone, and (b) a peripheral region comprisingmultiple segments and having a discontinuous wavefront cross-sectionphase profile having phase shifts between segments that are equal to thedesign wavelength or multiples of the design wavelength, wherein thephase shifts in the peripheral region are less than or equal to thewavefront maximum height in the central zone; and wherein the at leastone laser-modified layer forms at least part of at least one of thecentral zone or the peripheral region.
 19. The method of claim 18,wherein the at least one laser-modified layer includes a portion havinga continuous variation in index of refraction forming the central zone.20. The method of claim 18, wherein the at least one laser-modifiedlayer includes portions having discontinuous variations in index ofrefraction forming the peripheral region.
 21. A method for modifying arefractive property of ocular tissue in an eye, comprising: forming atleast one optically-modified layer in at least one of the corneal stromaand the crystalline lens ocular tissue in an eye by scanning lightpulses from a laser focused in the corneal stroma or crystalline lensocular tissue along regions of the corneal stroma or crystalline lensocular tissue to cause changes in the refractive index within the oculartissue to form a modified corneal stroma or crystalline lens; whereinthe modified corneal stroma or crystalline lens comprises (a) a centralzone having a continuous wavefront cross-section phase profile, having awavefront maximum height of greater than 1 design wavelength λ in thearea of the central zone, and (b) a peripheral region comprisingmultiple segments and having a discontinuous wavefront cross-sectionphase profile having phase shifts between segments that are equal to thedesign wavelength or multiples of the design wavelength, wherein thephase shifts in the peripheral region are less than or equal to thewavefront maximum height in the central zone; and wherein the at leastone optically-modified layer forms at least part of at least one of thecentral zone or the peripheral region.
 22. The method of claim 21,wherein the at least one optically-modified layer includes a portionhaving a continuous variation in index of refraction forming the centralzone.
 23. The method of claim 21, wherein the at least oneoptically-modified layer includes portions having discontinuousvariations in index of refraction forming the peripheral region.